Abstract: TH-PO304
Sodium Zirconium Cyclosilicate (SZC) Binds Ammonium (NH4+) in the GI Tract
Session Information
- Fluid, Electrolyte, and Acid-Base Disorders: Basic
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Fluid‚ Electrolyte‚ and Acid-Base Disorders
- 1001 Fluid‚ Electrolyte‚ and Acid-Base Disorders: Basic
Authors
- Marmol Mosquera, Fernando Anibal, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
- Badaruddin, Mohammed Qursheed Muzzammil, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
- Baig, Athar, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
- Ye, Minghao, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
- Wysocki, Jan, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
- Bamberg, Krister, Translational Science and Experimental Medicine, Early Cardiovascular, Renal and Metabolsim (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
- Batlle, Daniel, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
Background
Sodium zirconium cyclosilicate (SZC) is a non-absorbed, non-polymeric inorganic cation exchanger that selectively captures Potassium (K+) in the exchange for hydrogen (H+) and Sodium (Na+) in the gastrointestinal tract. The ionic diameter of NH4+ and K+ in aqueous solution are similar in size and both are bound by SZC in vitro, suggesting that SZC binds not only K+ but also NH4+ in the gastrointestinal tract. This hypothesis was studied in mice placed in metabolic cages to collect feces and urine for comparison of ammonium excretion concurrently on a regular diet followed a diet with added SZC.
Methods
Mice (CD-1 background) on a regular diet for 2 days were switched to a diet containing SZC (6g /Kg BW) for the following 3 days and placed in metabolic cages designed to collect urine and feces separately but simultaneously over a period of 6 hours to be able to assess fecal and urine NH4+ excretion. Feces NH4+ was measured using a non-enzymatic assay, where ammonia forms indophenol, a highly colored product easily quantifiable by colorimetry. In all fecal samples NH4+ was concurrently measured with and without 50 mEq KCl- solution to release NH4+ from SZC present in the feces.
Results
When SZC was added to the diet the fecal NH4+ excretion measured after release of NH4+ with KCl was significantly higher than in absence of KCl- (2.2 ±0.2 and 1.6 ±0.2 umol/6hrs), respectively p=0.0005 (fig, right panel). In the regular diet, used as a negative control, addition of KCl- to
the samples had no significant effect on measured fecal NH4+ (1.9 ±0.3 vs 1.8 ±0.3 umol/6hrs,p=0.55) (fig, left panel).
Conclusion
In feces from normal mice on a diet with added SZC there is a substantial amount of NH4+ sequestered in the K+ binder. This is consistent with the hypothesis that SZC binds NH4+ in the GI tract and hence may offer therapeutic opportunities on top of its known K+ binding action used to treat hyperkalemia.
Funding
- Commercial Support –